Performance of the World Health Organisation suspected COVID-19 case definition in cluster-associated and sporadic SARS-CoV-2 transmission in Malaysia.

INTRODUCTION: Cluster-associated transmission has contributed to the majority of COVID-19 cases in Malaysia. Although widely used, the performance of the World Health Organization (WHO) case definition for suspected COVID19 in environments with high numbers of such cases has not been reported. MATERIALS AND METHODS: All suspected cases of COVID-19 that self-presented to hospitals or were cluster screened from 1st April to 31st May 2020 were included. Positive SARS-CoV-2 rRT-PCR was used as the diagnostic reference for COVID-19. RESULTS: 540 individuals with suspected COVID-19 were recruited. Two-third of patients were identified through contact screening, while the rest presented sporadically. Overall COVID-19 positivity rate was 59.4% (321/540) which was higher in the cluster screened group (85.6% vs. 11.6%, p<0.001). Overall, cluster-screened COVID-19 cases were significantly younger, had fewer comorbidities and were less likely to be symptomatic than those present sporadically. Mortality was significantly lower in the cluster-screened COVID-19 cases (0.3% vs. 4.5%, p<0.05). A third of all chest radiographs in confirmed COVID-19 cases were abnormal, with consolidation, ground-glass opacities or both predominating in the peripheral lower zones. The WHO suspected case definition for COVID-19 accurately classified 35.4% of all COVID-19 patients, a rate not improved by the addition of baseline radiographic data. Misclassification rate was higher among the cluster-associated cases (80.6%) compared to sporadic cases (35.3%). CONCLUSION: COVID-19 cases in Malaysia identified by active tracing of community cluster outbreaks had lower mortality rate. The WHO suspected COVID-19 performed poorly in this setting even when chest radiographic information was available, a finding that has implications for future spikes of the disease in countries with similar transmission characteristics.

Lung cancer screening provides a unique opportunity for early diagnosis and management of interstitial lung diseases

P4 Table 1Characteristics of the subjectsCharacteristics Subjects with ILAs on LDCT (n = 39) Age, yr, mean (± SD) 68.8 (± 4.3) Gender, n (%) Female 15 (38.5) Male 24 (61.5) Smoking status, n (%) Current 7 (17.9) Ex 32 (82.1) Respiratory symptoms, n (%) None 19 (48.7) Cough 3 (7.7) Dyspnoea 9 (23.1) Cough & dyspnoea 6 (15.4) N/A 2 (5.1) Physical examination findings, n (%) None 5 (12.8) Crackles 17 (43.6) N/A 17 (43.6) Baseline lung function,%pred, median (range) FEV1,% pred 91 (58 – 130) FVC,% pred 94.8 (65 – 143) TLco,% pred 57.6 (28.4 – 98.8) Kco,% pred 79.5 (36.4 – 94) MDT Diagnosis ILAs, n (%) 8 (20.5) ILD, n (%) IPF 14 (35.9) Smoking-related ILD 6 (15.4) Hypersensitivity pneumonitis 4 (10.3) PPFE 3 (7.7) Sarcoidosis 1 (2.6) Post-COVID ILD 1 (2.6) Vasculitis 1 (2.6) Unclassifiable 1 (2.6) Treatment, n (%) Smoking cessation advice 6 (15.4) Antifibrotic 7 (17.9) Immunomodulatory treatment 2 (5.1) None 23 (59) ResultsILAs of >5% extent on LDCT were identified in 39/1853 (2.1%) subjects screened between August 2018 and April 2021 (table 1). Respiratory symptoms were present in 18/39 (46.1%) and crackles were auscultated in 17 of 22 subjects (77.3%) undergoing physical examination. Past exposure to potential environmental triggers was noted in 21/39 (53.8%). Diagnostic bronchoalveolar lavage was performed in 7/39 (17.9%) and one patient underwent transbronchial lung cryobiopsy. After MDT discussion, ILD was concluded in 31/39 (79.5%) cases, of which 14/31 (45.2%) were diagnosed with IPF. In the IPF subgroup, antifibrotics were initiated in 7/14 (50%) of cases. In those diagnosed with other ILDs, immunomodulatory treatment was initiated in 2/25 (8%) subjects.ConclusionA large proportion of individuals with newly identified ILAs have an abnormal clinical examination and respiratory symptoms, consistent with the widely held suspicion that ILD is underdiagnosed in the community. Lung cancer screening in this demographic provides a unique opportunity to address this unmet health metric. Earlier identification of ILD, specifically IPF, allows institution of antifibrotic therapies proven to modify the natural history of the disease by preserving lung function and extending life. The cost-effectiveness of this approach for ILD screening warrants detailed evaluation.

Prevalence of chronic cough following COVID-19 infection: A cross sectional study

Rationale: SARS CoV-2 infection has been associated with long-term sequelae, including cough. The clinical course of chronic cough following SARS CoV-2 infection and therapies are not known. This study examined the prevalence and characteristics of chronic cough following SARS CoV-2 infection, aiming to assess its course, impact on patient well-being and predisposing factors. Methods: 113 patients were analysed as part of PREDICT UK follow up (NHS HRA: 20/HRA/2344) at 3 to 6 months (mean 152 days) after admission for a PCR positive SARS CoV2 infection. The baseline clinical and demographic characteristics were examined to assess contributing mechanisms that may predispose to chronic cough (defined as >8 weeks following SARS CoV2 infection). Results: 41.5% patients did not have a cough. In contrast, 24% of patients had an acute cough (<3 weeks), 10.6% had subacute cough (3 to 8 weeks), and 21.6% had chronic cough (>8 weeks). 1.7% of patients had a pre-existing cough, unchanged following COVID-19. The demographic and clinical characteristics of the study population are summarised in Table 1.50% of the cough group had a pre-existing lung disease (mainly airways disease), compared to 16% of patients without cough (P < 0.001). No differences in hypoxia, inflammation or infection markers (CRP) were noted between the 2 groups at admission. Diffusion Capacity for Carbon Monoxide (DLCO) was significantly reduced in those with cough compared with the non-cough group (32.2% vs 57.7%;P = 0.02). No significant differences in cough was noted between patients treated with different ventilator support strategies i.e. ITU and CPAP vs simple oxygen supplementation. Conclusions: This study notes a prevalence of chronic cough in 21.6% of patients post COVID-19. This was not associated with airway obstruction, reducing the likelihood of post infective bronchoconstriction. There was a significant reduction in DLCO consistent with post-infective interstitial lung disease (ILD). This study has looked at first-wave patients where dexamethasone was minimally used. Future studies reviewing cough with steroids therapy in patients requiring oxygen supplementation may note reduced levels of chronic cough. The use of cough as marker of post- COVID ILD warrants investigation. The current findings are in keeping with previous reports in SARS and MERS, where DLCO impairments were noted with time resolution of up to two years.

Prognostication in covid-19: A prospectively Derived and externally validated risk Prediction score for in-hospital death

Introduction and Objectives The disease spectrum of COVID-19 ranges from mild viral illness to devastating lung injury that heralds the acute respiratory distress syndrome. Different risk factors of adverse outcomes have been identified but prospectively stratified and externally validated studies of prognosis are lacking. We set out to identify independent predictors of mortality and to develop and validate a clinically applicable risk prediction model of COVID-19. Methods 983 consecutive patients with COVID-19 were prospectively recruited over an 11-week period for an outcome of in-hospital death. Multiple imputation was used to address randomly missing data. 12 independent mortality predictors were identified by multivariate regression and internally validated by bootstrapping. A prognostic score was constructed and validated in an external cohort (N=277) and assessed for predictive accuracy including goodness-of-fit by the Hosmer-Lemeshow test. Results The median age of the derivation cohort was 70 (IQR: 53-83). Among non-survivors (29.9%;294/983), the highest odds ratios for death (with 95% confidence intervals) were age >70 (7.65;4.89-11.98;P<0.001), BMI >30 (2.39;1.88-3.03;P<0.001), baseline hypoxia (2.24;1.78-2.79;P<0.001), chronic kidney disease stage 5 (2.00;1.18-3.41;P<0.05) and tachypnoea (1.79;1.43-2.24;P<0.001). White ethnicity accounted for 85% of all nonsurvivors (P<0.01 vs. non-White ethnicities). Care home residency was associated with an increased risk of COVID-19 death on univariate analysis (OR 3.14;95% CI: 2.28-4.32). A linear relationship between increasing COVID-19 severity and in-hospital mortality was derived from the development dataset. Evaluation of a risk score (ranging 1-19 points) disclosed good discriminatory ability (area under the receiver operating characteristic 0.855), sensitivity (59.7%), specificity (87.6%), positive predictive (70.2%) and negative predictive value (81.6%). Subsequent validation of the score in an age and mortality-matched independent cohort showed robust performance parameters: Accuracy/AUC 0.797, calibration slope (R2) of 0.882 (see calibration belt figure 1). Conclusions Integration of key variables including age, indices of acute respiratory illness and comorbidities into a clinical risk score allows in-hospital death due to COVID-19 to be reliably predicted. The ability to risk stratify may help frontline clinicians in decision processes in respect of escalation and de-escalation strategies during resurgent COVID-19.

P256 Prognostication in COVID-19: a prospectively derived and externally validated risk prediction score for in-hospital death

P256 Figure 1ConclusionsIntegration of key variables including age, indices of acute respiratory illness and comorbidities into a clinical risk score allows in-hospital death due to COVID-19 to be reliably predicted. The ability to risk stratify may help frontline clinicians in decision processes in respect of escalation and de-escalation strategies during resurgent COVID-19.